Reusable Liquid Chromatographic Columns

ABSTRACT

A reusable liquid chromatographic column consists of three parts, a column body with an integral outlet port molded on one end, a sealing insert with an inlet port, and a perforated cap providing downward force to compress the sealing insert into the column body. A wedge-like seal is employed to seal the connection between the sealing insert and the column body. Two filters on both ends of the column body are used to prevent escape of packing materials from the column chamber under pressure. Hand tightening is adequate to seal the connection by screwing the perforated cap onto the column body. The column is reusable due to its simple disassembling and reassembling processes. It is also disposable due to its inexpensive fabricating materials and manufacturing process.

BACKGROUND OF THE INVENTION

The invention relates to liquid chromatographic columns and methods ofassembling and disassembling reusable, economic, and leak-freechromatographic columns.

Liquid chromatography is an analytical chromatographic technique that isbased on differences in partitioning behaviors between a mobile phaseand a stationary phase to separate the components in a mixture, morespecifically, to separate ions or molecules dissolved in a solvent. Acolumn is packed with the stationary phase and the mobile phase carriesthe mixture through it. Sample components having stronger affinity withthe stationary phase spend longer time in the column and are separatedfrom components that have weaker affinity with the stationary phase andpass through the column faster.

In pursuit of optimal separation, the chromatography system is usuallyoperated under pressure to facilitate the flow of the mobile phase inthe stationary phase. As a consequence, the columns demand effectiveseals to prevent the mobile phase from leaking out of the pressurizedpassage. An O-ring employed in some prior art methods (U.S. Pat. No.5,601,708 and U.S. Pat. No. 6,436,284) can provide a good seal for theopenings of the column, but some organic solvents used as a mobile phasein liquid chromatography can damage the O-ring after a lengthy soakingin the solvents. The methods for making commercially availabledisposable columns (U.S. Pat. No. 6,565,745 and 6,949,194) involve theuse of a snap-on cap to form a sealing connection between the columnbody and the sealing head. This technique could lead to sealing failureunder substantial pressure build-up. In addition, the use of snap-on capwith cantilever members and the ramped detents molded on the column bodyforms a tight interference fit, which practically makes the columnsolely for one-time use due to the inability in disassembling column forrepeated uses. Columns made of glass (U.S. Pat. No. 6,811,688) cannotwithstand a pressurized system and cost more than plastic columns. Otherprior art technique (U.S. Pat. No. 6,797,174) requires a complicatedprocess involving six separate pieces and one spacer ring. Alow-pressure liquid chromatographic cartridge is provided with aresilient fluid tight seal (US Patent Application 2005/0247632), but therotation resulted from threading the cap onto the cartridge containercould cause seal failure and the cartridge is not reusable.

All these prior art techniques have the drawbacks of high cost forcolumn assembly, seal failure, or one-time use. It is the object of thisinvention to provide reusable, economic, and leak-proof liquidchromatographic columns for the separation and purification of organiccompounds.

SUMMARY OF THE INVENTION

The invention is aimed at providing reusable, economic and leak-proofliquid chromatographic columns. It is still aimed at providing a simple,but reliable process to assemble and disassemble the columns. In oneaspect, the columns can be reusable since the assembly and disassemblyprocesses are easy to fulfill without assistance from special devices ormachines. Conventional tools, such as pliers, wrenches, and tweezers,are adequate to disassemble and assemble the columns. In another aspect,the columns are also disposable due to its inexpensive materials andsimple assembly process.

The column includes three separate parts, a cylindrical body with oneend having one port molded as a single piece to the body and the otherend with an opening for loading the packing material and sealing, asealing insert molded with another port directed toward the bodychamber, and a perforated cap used to force the sealing insert into thecolumn body by use of hand-tightening. At the both ends of the packingmaterial loaded in the column chamber, two filters are employed toprevent the packing material from entering the ports.

In the preferred embodiment, a wedge-like seal is adopted to theconnection between the column body with a tapered rim on the inner walland the sealing insert with a conical circumference. The outer wall onthe opening portion of the column body is molded with male threads forthe perforated cap comprising female threads. The sealing insert, alongwith the perforated cap around it, is placed into the column body. Byturning the cap onto the column base, the perforated cap providesstraight downward force to push the sealing insert into the column bodyto form a compression type fitting. The perforated cap has small ridgeson the outer wall to aid in gripping and hand-tightening with ease.

One of the advantages and features of this invention is the columndesigned for repeated uses. Although the used column is disposable, itcan afford multiple uses with appropriate disassembling and reassemblingprocesses. The used column is readily disassembled by unscrewing theperforated cap, pulling out the sealing insert, and then removingfilters and the packing material. After reloading with new packingmaterial and filters into the used column body, the used sealing insertand perforated cap are reassembled onto the column body to form a newcolumn with tight seal. A column in this embodiment can be reused up toten times, preferably two to three times with replacement of new packingmaterial and filters each time. The number of using times is subject tothe integrity of the sealing interface between the sealing insert andthe column body. A smooth surface free of cracks or niches isindispensable for the column reassembly. The inventedliquid-chromatographic columns can sustain relatively high pressure upto 180 psi.

The column may also be disposable thanks to its inexpensive fabricatingmaterial, such as polyethylene, polypropylene, and its economicassembling process. Packing materials include silica, silica gel,alumina, regenerated silica, regenerated silica gel, regeneratedalumina, and the like. Hand-tightening without or with slight assistancefrom wrenches or pliers is sufficient to provide reliable seal undersubstantial internal pressure. Other advantages of this invention willbe described in the preferred embodiment thereof and from the claims.

DESCRIPTION OF THE DRAWINGS

For the purpose of easy understanding the advantages this inventionbrings, the following seven drawings are used to explicitly describe thecolumn features and the assembling and disassembling processes.

FIG. 1 is a perspective view of the whole column based on thisinvention;

FIG. 2 is an exploded cross-sectional view of the column of FIG. 1;

FIG. 3 is a fragmentary sectional view of the sealing part;

FIG. 4 is a perspective view of the sealing insert (Type I);

FIG. 5 is a cross-sectional view of the sealing insert of FIG. 4;

FIG. 6 is a perspective view of the sealing insert (Type II); and

FIG. 7 is a perspective view of the perforated cap.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 shows a perspective view of the whole column in this embodiment.The chromatographic column 10 with a cylindrical structure has a sealinginsert 18 with a molded inlet port 14, a perforated cap 20, and a columnbody 12 with a molded outlet port 16. The packing material is loadedinside the column chamber 13. In the operation procedure, the inlet port14 is connected to a source where the mobile phase flows into the column10. The mobile phase carries mixture from the inlet port 14 to outletport 16 through the packing material in which components are separateddue to different retention times caused by the difference in affinity ofeach component to the packing material. The outlet port delivers theseparated components to a detecting device to identify or quantify eachcomponent, which is finally collected in containers. The size of thecolumn 10 varies with the amount of separated samples.

Referring to FIG. 2, it is seen that the column 10 has five pieces insequence: a perforated cap 20 with an opening 56, a sealing insert 18with an inlet port 14, an inlet filter 22, an outlet filter 24, and acolumn body 12 molded with an outlet port 16. The cylindrical chamber 13is for filling the packing material, such as silica gel. Two filters 22and 24, porous frit, are placed on the two ends of the column chamber 13to avoid the leaks of the packing material from the column body 12. Theinlet port 14 is integrally molded on the sealing insert 18, which isplaced into the open end of the column body in the assembling process. Aperforated cap 20 with female threads 54 is used to fix the sealinginsert 18 into the column body 12 with a sealing connection.

The sealing connection of the apparatus is shown in FIG. 3. Thewedge-like seal is used to form a tight seal at the inlet end. The inletopening of the column body 12 consists of a tapered end 26, whichreceives a slope 36 on the sealing insert 18 to form the sealingsurface. The perforated cap 20 is placed onto the sealing insert 18 toprovide downward force to push the sealing insert 18 into the columnbody 12 by screwing down the perforated cap onto the column body. Inthis sealing connection, the perforated cap 20 with female threads 54plays a role as a nut with female threads and the column body 12 is likea hollow bolt with male threads 28 on the outer wall. The sealing insert18 is forced to move linearly downward into the column body 12 withouttangential rotating movement. A compression-type fitting is formedbetween the slope 36 of the sealing insert 18 and the tapered rim 26.The use of threads in the connection allows easy disconnection of theperforated cap 20, the sealing insert 18, and the column body 12 withoutdamaging the sealing interface. The outer diameter of the step 44 of thesealing insert 20 is sized to fit within the perforation opening 56 ofthe perforated cap 20 with minimum radial clearance of 0.01 mm to 10 mmbetween the two. The clearance leads to easy operation and avoidstangential rotating movement between the sealing insert 18 and thetapered end 26 during the cyclic operation of assembly, disassembly, andreassembly. The design aimed at easy disassembly and reassembly of thecolumn provides a base for reusing the column with multiple times.

FIG. 4 shows a conventional design (Type-I) for the insert 18. The inletport 14 has a female luer fitting with partial male threads 40 toconnect to a source where the mobile phase flows through.Finger-tightening is adequate to connect the inlet port to the source ofthe mobile phase by turning the fitting on. Referring to FIG. 5, theradius of the circumferential stair 32 is extended to be a little largerthan the inner radius of the opening of the column body 12 in avoidanceof the whole sealing insert 18 entering the column body 12. A side slope36 with an angel from 5 to 75°, preferably from 10 to 50°, mating thesurface of the tapered end 26 allows the sealing insert 18 to slide intothe column body 12. Three stairs 38, 42 and 44 are employed to reinforcethe hardness and mechanical strength of the inlet port. Although thestairs with other numbers of more than three or less than one (no stair)can be used, two to three stairs are preferred in the invention forrepeated uses. The height of the stair 38 is equal to the height of thecircumferential stair 32 in order to receive even downward force in thecenter and on the edge of the sealing insert 18. The use of the recess46 between stair 38 and 32 is aimed at saving materials and avoiding theinsert deformation caused by thick layer in the molding process.

As shown in FIG. 5, a conical shape 48, which is open toward the inletfilter 22 at the end the inlet passage, is designed to allow evendispersion of fluid cross the filter 22 and the packing materials in thecolumn body 12. The sealing insert 18 has an additional circularprotrusion 50 on the rim of the insert bottom 51. The protrusion with aheight of 1.5 mm (e.g. 0.5 to 5 mm, preferably 1 to 3 mm) has a 75°angel (e.g. 30 to 150°, preferably 60 to 120°) in section and protrudesdownward from the surface 51. After compressed downward, the protrusion50 can dig into the filter 22, which is tightly against the walls of thecolumn body 12 to stop the movement of packing materials under pressure,to form a seal in case that any defect fitting between the filter 22 andthe column wall cause the leaks of the packing material. Accordingly,another protrusion 25 with the size equal to the protrusion 50 ispositioned against the filter 24 at the outlet end to prevent leaks ofthe packing material to the outlet port 16. The disk-shaped filters 22and 24 are made of porous polymer with elasticity for receiving pressingfrom the protrusions 50 and 25, respectively.

An alternative design (Type-II) for the sealing insert is shown in FIG.6. The sealing insert 19 has radial spokes 45A-45F with a number of 6(e.g. 2 to 16, preferably 4 to 12). The spokes 45A-45F molded on thebottom 43 of the sealing insert 19 are used to increase the mechanicalstrength of the bottom 43 and enable the bottom to withstand substantialinternal pressure. The spoke height is lower than that of thecircumferential step 41. The spokes 45A-45F are extended from the stair39 outwardly, but not reach to the wall of the circumferential step 41.The space between the end of each spoke and the wall is intended to makethe sealing slope receive the even force from the tapered rim 26. Stairs37 and 39 are used to reinforce the mechanical strength of the insetport 14. This spoke-molded insert is preferably designed for a big sizecolumn, which has a large contact surface between the sealing insert andthe filter 22. The bottom surface 43 integrated with spokes of thesealing insert 19 can prevent deformation under high internal pressure.The radial spokes can also be employed to increase the mechanicalstrength of the bottom 58 at the outlet of the column body 12 for thesake of high internal pressure tolerance.

The compressive force applied to pushing the sealing insert 18 downwardis provided from the perforated cap 20 by screwing it onto the columnbody 12. FIG. 7 shows the perspective view of the perforated cap 20,which functions as a nut with female threads 54. The knurls 52, regularsmall ridges on the outer surface of the perforated cap 20, assist toprevent slipping while the connection is tightened by hands throughgripping the perforated cap 20. Referring to the cross-sectional view ofthe column 10 in FIG. 2, female threads 54 along with male threads 28 onthe outer wall of the column body 12 can be clockwise orcounter-clockwise. A perforation 56 sized between the diameters of thestair 44 and the stair 38 is formed on the top of the cap 20 to ensurethat the downward force is evenly scattered on the stairs 32 and 38 ofthe insert 18. The connection with separate sealing insert 18 andperforated cap 20 provides only straight linear movement between theslope 36 and the tapered end 26 instead of tangential movement, whichcan cause abrasion and defects at the sealing interface and eventuallygive rise to a failed seal.

In the packing process of a chromatographic column, the filter 24 withthe diameter equal to the bottom size of the column body 12 is firmlyplaced against the protrusion 25. The packing materials are introducedto the column chamber 13 with the assistance of vacuum hooked to theoutlet port, or just by vibrating the column body 12 to ensure thepacking materials closely packed inside the column chamber. Any voidvolume in the packing materials should be prohibited since it can leadto poor separation efficiency. After the packing material nearly reachesto the tapered end 26, the inlet filter 22 is placed on the top of thepacking material layer. The sealing insert 18 is then inserted into thetapered end 26. Once the perforated cap 20 is aligned onto the sealinginsert 18, the connection can be firmly formed by turning the perforatedcap 20 onto the column body 12. A wrench or a pair of pliers may beapplicable to aiding tightening, but hand tightening is adequate toassemble the column with tight seal.

The column allows a number of repeated uses since it can be easilydisassembled and reassembled with hands. After the packing material inthe used column is dry, the perforated cap 20 is readily unscrewed fromthe column body 12. The filters 22 and 24, as well as the packingmaterial, are then removed from the column chamber 13. Three partsincluding the perforated cap 20, the sealing insert 18, and the columnbody 12, can be cleaned with organic solvents for the next use. Withreplacement of the packing material and two filters, a new column can beeasily reassembled according to the assembling process described above.During the assembling and disassembling process, the contact surfaces ofthe tapered end 26 and the slope 36 should be kept clean, smooth, andfree of any cracks or niches. The column can be used up to ten timeswith care of three reusable parts, the perforated cap 20, the sealinginsert 18, and the column body 12.

In this design, the sealing connection consisting of the sealing insert18 and the perforated cap 20 performs as an inlet end, as describedabove. However, in the preferred embodiment, the inlet port 14 andoutlet port 16 can switch positions if the female luer fitting withpartial male threads 40 is molded on the column end 16. As aconsequence, the sealing connection would be on the outlet end. Themobile phase would flow into the column through the molded end and flowout of the column through the sealing connection end. Indeed, such anupside-down design would enhance the column resistance against leaksunder a pressurized system since the outlet pressure is always lowerthan the inlet pressure. The preferred embodiments and illustrativedetails set forth should merely be regarded as descriptive disclosure.Various other changes and additions in the form and detail thereof maybe made therein without departing from the spirit and scope of theinvention.

1. A chromatographic column comprising: a tubular column body having aninlet end with an opening for loading the packing materials and sealingand the other end with an outlet port molded as a single piece onto saidcolumn body for the mobile phase flowing out, said column body having achamber to fill with the packing material from said inlet end, saidcolumn body having male threads on the outer wall of said inlet end; asealing insert with a molded inlet port and a side sealing slopeallowing said sealing insert to slide into said inlet end of said columnbody to form a wedge-like seal; a perforated cap with ridges on saidouter surface and female threads on said inner surface; two filters withone filter placed in said outlet end of said column body and anotherfilter placed on said inlet end of said column body.
 2. Thechromatographic column of claim 1 wherein said inlet end has a taperedrim surrounding the inner wall of said inlet end of said column body. 3.The chromatographic column of claim 1 wherein said male threads on saidouter wall of said column body fit said female threads on said innerwall of said perforated cap to form a nut-bolt assembly.
 4. Thechromatographic column of claim 1 wherein said sealing insert has acenter step to evenly share compression with the peripheral edge.
 5. Thechromatographic column of claim 1 wherein said sealing insert has spokeswith a number of between 2 and 16 to reinforce the strength of thebottom of said sealing insert.
 6. The chromatographic column of claim 1wherein said sealing insert has a circumferential side slope with anangel of between 50 and 75°.
 7. The chromatographic column of claim 1wherein said column body has a circumferential protrusion with an angelof between 30° and 120° on said outlet end inside said column body. 8.The chromatographic column of claim 1 wherein said perforated cap has aknurled outer surface including, but not limited to ridges.
 9. Thechromatographic column of claim 1 wherein said perforated cap is used toprovide downward force to push said sealing insert into said column bodyby screwing said perforated cap onto said column body.
 10. Thechromatographic column of claim 2 wherein said tapered rim hassufficiently smooth inner surface.
 11. The chromatographic column ofclaim 7 wherein said circumferential side slope has sufficiently smoothouter surface.
 12. The chromatographic column of claim 1 wherein saidwedge-like sealing structure is formed between said tapered rim of claim12 and side slope of claim
 13. 13. The chromatographic column of claim 1wherein said parts including said column body, said sealing insert, andsaid perforated cap are made of plastic.
 14. The chromatographic columnof claim 1 wherein said filters are porous frits made of porouspolymers.
 15. The chromatographic column of claim 1 wherein said inletport can be molded on said column body to become an outlet port and saidoutlet port can be molded on said sealing insert to become an inletport; i.e. wherein said inlet port and said outlet port can switchpositions.
 16. A method of assembling a chromatographic columncomprising the steps of: placing the outlet filter in said outlet endhaving an integrally molded outlet port; filling said column chamberwith the packing material up to said inlet end of said column body;placing the inlet filter on top of the packing material at said inletend; placing said sealing insert on top of the second filter; aligningsaid perforated cap on said sealing insert; and turning said perforatedcap onto said column body until the connection is firmly formed.
 17. Themethod of claim 16 wherein hand tightening is used to turn saidperforated cap onto said column body.
 18. The method of claim 17 whereinhand tightening is assisted with common tools including, but not limitedto wrenches and pliers.
 19. The method of claim 16 in which the step ofturning said perforated cap onto said column body provides compressionof said sealing insert into said inlet end of said column body withdownward linear motion without involvement of relative rotation to saidtapered rim.
 20. A method of disassembling a chromatographic columncomprising the steps of: unscrewing said perforated cap from said columnbody; pulling out said sealing insert from said column body; removingsaid inlet filter from the top of the packing material; emptying saidcolumn chamber by vibrating or digging out the packing material;removing said outlet filter from said outlet end; disposing the packingmaterial and said two filters; and cleaning said column body, saidsealing insert, and said perforated cap for repeated uses.
 21. Themethod of claim 20 in which steps are used for repeated use of saidchromatographic column.
 22. The method of claim 16 in which steps areused for reassembling said chromatographic column by reloading newpacking material and replacing two filters with new ones.